A Review: Treatment of Alzheimer’s Disease Discovered in Repurposed Agents

Appleby, Brian S.; Nacopoulos, Dimitrios A.; Milano, Nicholas; Zhong, Kate; Cummings, Jeffrey L.

doi:10.1159/000345791

Cited by 74 publications

(74 citation statements)

References 306 publications

(187 reference statements)

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“…It could also potentially improve the assessment of the probability of disease progression and specific treatment strategies could be adapted, as more invasive and potentially harmful disease-modifying treatments for AD become available [165]. …”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Hommet

Mondon²,

Camus³

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying β amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The translocator protein (TSPO) is upregulated during neuroinflammation. Consequently, targeting TSPO with radiolabeled ligands for PET is an attractive biomarker for neuroinflammation. Methods: A review of the research literature on PET imaging which studied in vivo neuroinflammation in AD subjects and its relationship with amyloid load was performed, including papers published between 2001 and 2012. Results: Six studies were included using either [¹¹C]PK-11195 or another non-TSPO radioligand that binds to the monoaminooxidase B. All the studies evaluated amyloid load with [¹¹C]PIB. Microglial activation and astrocytosis are potentially early phenomena in AD. However, the individual levels of amyloid deposition and microglial activation were not correlated. Conclusion: Noninvasive in vivo molecular imaging to visualize neuroinflammation in AD may contribute to our understanding of the kinetics of neuroinflammation and its relationship to the hallmarks of the disease. Both are important for the development of future therapeutic modalities and for quantifying the efficacy of future disease-modifying treatments.

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Section: Discussionmentioning

confidence: 99%

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Hommet

Mondon²,

Camus³

et al. 2013

Dement Geriatr Cogn Disord

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“…Dementia medications and medications a) whose use has been suggested as repurposed agents in dementia in Appleby et al 2013 [21], and b) are prescribed within the UK mental health care setting. The complete list of medications extracted can be found in S1 Table.…”

Section: Methodsmentioning

confidence: 99%

Trajectories of dementia-related cognitive decline in a large mental health records derived patient cohort

et al. 2017

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BackgroundModeling trajectories of decline can help describe the variability in progression of cognitive impairment in dementia. Better characterisation of these trajectories has significant implications for understanding disease progression, trial design and care planning.MethodsPatients with at least three Mini-mental State Examination (MMSE) scores recorded in the South London and Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories of cognitive decline were identified through latent class growth analysis of longitudinal MMSE scores. Demographics, Health of Nation Outcome Scales and medications were compared across trajectories identified.ResultsFour of the six trajectories showed increased rate of decline with lower baseline MMSE. Two trajectories had similar initial MMSE scores but different rates of decline. In the faster declining trajectory of the two, a higher incidence of both behavioral problems and sertraline prescription were present.ConclusionsWe find suggestive evidence for association of behavioral problems and sertraline prescription with rate of decline. Further work is needed to determine whether trajectories replicate in other datasets.

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“…High levels of anxiety and depression may cause the cognitive profile of an individual with AD to appear worse than that caused by AD pathology, and the usefulness of anxiolytics and anti-depressants must be considered (Appleby et al 2013;Henry et al 2011). These and other influencing factors will be discussed further below.…”

Section: Individual Rates Of Declinementioning

confidence: 99%